Olfactory function is disturbed in schizophrenia, as identified by behavioral markers (smell identification and odor threshold) and olfactory event-related potentials (OERPs). These disturbances are also present in unaffected family members, which make them good candidates as potential biomarkers of schizophrenia risk. Smell identification deficits were found to discriminate who among high-risk cases will actually develop schizophrenia. Little is, however, known about the underlying pathophysiology of emerging psychosis during the prodromal period. This R21 application brings together clinical researchers doing prodromal studies and investigators with expertise in cognitive and electrophysiologic studies in schizophrenia. The proposed study will use improved methods for ERP analyses and for identifying at-risk young people so as to evaluate in cross-section behavioral and electrophysiological measures of olfactory function in prodromal patients, and their association with symptom features and measures of social and cognition function. If olfactory ERPs are found to be abnormal in prodromal patients, we will then apply for an R01 to evaluate whether olfactory ERPs in a prodromal cohort may be a biomarker of conversion to schizophrenia. ERPs and behavioral detection responses will be measured in 30 prodromal patients and 30 matched healthy controls to three concentrations of hydrogen sulfide during a detection task. This will take advantage of existing methods for precise control of olfactory stimuli (olfactometer) and also new data analytic techniques in the electrophysiologic domain. Current source density (CSD;surface Laplacian) and temporal principal components analysis (PCA) are combined to yield reference-free measures of radial current flow corresponding to meaningful olfactory ERP components. Auditory ERPs will also be measured during a novelty oddball detection task so as to begin to examine the modality specificity of olfactory ERP deficits. Interviewer-based and self-ratings of psychopathology, measures of social function, facial emotion recognition, and cognitive function will be used to examine the relation of ERP and behavioral olfactory deficits in patients to prodromal symptoms, social function, and cognition. PUBLIC HEALTH RELEVANCE: From a clinical perspective, the study of prodromal patients is of importance not only for discovering markers for predicting conversion to schizophrenia but also for the potential development of treatments that would precede the onset of psychosis. Identification of a risk biomarker could lead to a lower rate of false positives in prodromal research and perhaps protect young people against unnecessary medication exposure.